The potential of mitochondrially-targeted tetrapeptide in protecting against noise-induced hearing impairment.

Abstract

Noise-induced hearing loss (NIHL) constitutes a significant global health issue for which there is no effective treatment. The loss of cochlear hair cells and associated synaptopathy are common causes of hearing impairment. One primary mechanism implicated in NIHL is the accumulation of reactive oxygen species (ROS), which ultimately overwhelms cochlear cells. ROS are detected in the cochlea immediately after noise exposure and persist for at least a week. Within cells, ROS are primarily generated in mitochondria as byproducts of cellular metabolism. Elamipretide is a synthetic tetrapeptide known to concentrate in mitochondria, improving mitochondrial function and reducing ROS production. To test the hypothesis that elamipretide treatment mitigates NIHL, 16-week-old male and female CBA/J mice were exposed to 8-16 kHz octave-band noise (OBN) at 98 dB SPL for 2 hours. Elamipretide was administered intraperitoneally immediately after noise exposure and continued for 2 weeks. Efficacy was evaluated based on auditory brainstem response (ABR) thresholds, wave amplitudes, and wave latencies in treated and control groups. Results showed that OBN-exposed mice exhibited an elevation in ABR thresholds at 16 and 32 kHz and a reduction in ABR wave-I amplitude at 32 kHz, although wave-I latencies were not affected at 16 or 32 kHz. Elamipretide treatment prevented the OBN-induced elevation of ABR thresholds and the attenuation of wave-I amplitude. These findings provide proof of concept that mitochondrial-targeted elamipretide can prevent NIHL in a mammalian model and highlight its potential to protect against NIHL in humans.